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Volume 20, Issue 3, Pages 156-163 (July 2010)


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The Tumor Microenvironment in Non–Small-Cell Lung Cancer

Edward E. Graves, PhD, Amit Maity, MD, PhDCorresponding Author Informationemail address, Quynh-Thu Le, MDCorresponding Author Informationemail address

The tumor microenvironment (TME) of NSCLC is heterogeneous with variable blood flow through leaky immature vessels resulting in regions of acidosis and hypoxia. Hypoxia has been documented in NSCLC directly by polarographic needle electrodes and indirectly by assessing tissue and plasma hypoxia markers. In general, elevated expression of these markers portends poorer outcomes in NSCLC. Impaired vascularity and hypoxia can lead to increased metastasis and treatment resistance. Compounds that directly target hypoxic cells such as tirapazamine have been tested in clinical trials for NSCLC with mixed results. Preclinical data, however, suggest other ways of exploiting the abnormal TME in NSCLC for therapeutic gain. The inhibition of hypoxia-inducible factor-1α or vascular endothelial growth factor may increase local control after radiation. Inhibitors of the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway, such as erlotinib or PI-103, may “normalize” tumor vessels, allowing for increased chemotherapy delivery or improved oxygenation and radiation response. To select patients who may respond to these therapies and to evaluate the effects of these agents, a noninvasive means of imaging the TME is critical. Presently, there are several promising modalities to image hypoxia and the tumor vasculature; these include dynamic perfusion imaging and positron emission tomography scanning with radiolabled nitroimidazoles.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA

Corresponding Author InformationAddress reprint requests to Amit Maity, MD, PhD, Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Bldg., 3620 Hamilton Walk, Philadelphia, PA 19104

Corresponding Author InformationQuynh-Thu Le, MD, Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Dr., MC 5847, Stanford, CA 94305

 Supported by NIH R01 CA093638 (AM), NIH R01 CA131199 (EG), and NIH PO1 CA67166 (Q-TL).

 Q-TL received research funding from GlaxoSmithKline, Amgen, and Varian for investigator initiated studies unrelated to the discussed topics.

PII: S1053-4296(10)00011-1

doi:10.1016/j.semradonc.2010.01.003


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